Alcohol consumption and risk of breast and ovarian cancer: A Mendelian randomization study

Abstract

BackgroundAlcohol consumption has been found to increase the risk of breast cancer in observation studies, yet it remains unknown if alcohol is related to other hormone-dependent cancers such as ovarian cancer. No Mendelian randomization (MR) studies have been performed to assess a potential causal relationship between alcohol use and risk of breast and ovarian cancer. MethodsWe aim to determine if alcohol consumption is causally associated with the risk of female hormone-dependent cancers, by using summary level genetic data from the hitherto largest genome-wide association studies (GWAS) conducted on alcohol consumption (N=~1.5 million individuals), breast (Ncase=122,977) and ovarian cancer (Ncase=25,509). We examined three different alcohol intake exposures, drinks per week (drinks/week), alcohol use disorder (AUD) and age-adjusted alcohol use disorder identification test (AUDIT-C), to reflect the general and harmful drinking behavior. We constructed updated and stronger instruments using ninety-nine drinks/week-related SNPs, nine AUD-related SNPs and thirteen AUDIT-C-related SNPs and estimated the causal relationship applying several two-sample MR methods. ResultsWe did not find any evidence to support for a causal association between alcohol consumption and risk of breast cancer [ORdrinks/week=1.01 (0.85–1.21), P=0.89; ORAUD=1.04 (95%CI: 0.89–1.21), P=0.62; ORAUDIT-C=1.07 (0.90–1.28), P=0.44]; neither with its subtypes including ER-positive and ER-negative breast cancer, using any of the three alcohol-related exposures. For ovarian cancer, however, we identified a reduced risk with alcohol consumption, where a borderline significance was found for AUDIT-C but not for drinks/week or AUC [ORdrinks/week=0.83 (0.63–1.10), P=0.19; ORAUD=0.92 (0.83–1.01), P=0.08; ORAUDIT-C=0.83 (0.71–0.97), P=0.02]. The effect attenuated to null excluding SNPs associated with potential confounders [ORdrinks/week=0.81(0.53–1.21), P=0.31; ORAUD=0.96(0.78–1.18), P=0.68; ORAUDIT-C=0.89(0.68–1.16), P=0.38]. ConclusionWe do not find any compelling evidence in support for a causal relationship between genetically predicted alcohol consumption and risk of breast or ovarian cancer, consistent across three different alcohol-related exposures. Future MR studies validating our findings are needed, when large-scale alcohol consumption GWAS results become available.